A role for ATP-sensitive potassium channels in male sexual behavior.
ATP-sensitive potassium (K(+)(ATP)) channels regulate cell excitability and are expressed in steroid-responsive brain regions involved in sexual behavior, such as the preoptic area (POA) and medial basal hypothalamus (MBH). We hypothesized that K(+)(ATP) channels serve as a mechanism by which testosterone can control the electrical activity of neurons and consequently elicit male sexual responsiveness. RT-PCR analysis indicated that castration induces, while testosterone inhibits, mRNA expression of the K(+)(ATP) channel subunit Kir6.2 in both the POA and MBH of adult male rats. Intracerebral infusion of the pharmacological K(+)(ATP) channel inhibitor tolbutamide increased the proportion of long-term castrates displaying sexual behavior and restored mount frequency, intromission frequency, and copulatory efficacy to values observed in testes-intact animals. Infusions of tolbutamide, but not vehicle, also decreased latencies to mount and intromit in castrated males. Unilateral tolbutamide infusion directly into the POA significantly reduced mount latency of castrates; however, it did not affect other copulatory measures, suggesting that blockade of K(+)(ATP) channels in additional brain regions may be necessary to recover the full range of sexual behavior. These data indicate that blockade of K(+)(ATP) channels is sufficient to elicit the male sexual response in the absence of testosterone. Our observations are consistent with the hypothesis that testosterone modulates male sexual behavior by regulating K(+)(ATP) channels in the brain. Decreased channel expression or channel blockade may increase the excitability of androgen-target neurons, rendering them more sensitive to the hormonal, chemical, and somatosensory inputs they receive, and potentially increase secretion of neurotransmitters that facilitate sexual behavior.
McDevitt
Melissa A
MA
Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
Thorsness
Robert J
RJ
Levine
Jon E
JE
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009919:Orchiectomy; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D013739:Testosterone / Q000008:administration & dosage / Q000378:metabolism*; D014044:Tolbutamide / Q000008:administration & dosage; D000099161:Kcnj11 Channel
D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D013739:Testosterone; D014044:Tolbutamide; D000099161:Kcnj11 Channel